Sulforaphane to Inhibit Myostatin? 3


In closing, lets bring in its ability to act as a significant anti-inflammatory and anti-cancer agent. I would like to look at three pieces of literature. The first is on the inhibition of histone deacetylase 6 acetylates and disrupts the chaperone function of heat shock protein 90: a novel basis for antileukemia activity of histone deacetylase inhibitors by Bali et al. The second is on  histone deacetylase inhibitors: signalling towards p21cip1/waf1 from Matthias Ocker. The third and final is entitled “A novel mechanism of chemoprotection by sulforaphane: inhibition of histone deacetylase” from Myzak et al. The hydroxamic acid (HAA) analogue pan-histone deacetylase (HDAC) inhibitors (HDIs) LAQ824 and LBH589 have been shown to induce acetylation and inhibit the ATP binding and chaperone function of heat shock protein (HSP) 90. This promotes the polyubiquitylation and degradation of the pro-growth and pro-survival client proteins Bcr-Abl, mutant FLT-3, c-Raf, and AKT in human leukemia cells. HDAC6 is a member of the class IIB HDACs. It is predominantly cytosolic, microtubule-associated alpha-tubulin deacetylase that is also known to promote aggresome inclusion of the misfolded polyubiquitylated proteins. Here we demonstrate that in the Bcr-abl oncogene expressing human leukemia K562 cells, HDAC6 can be co-immunoprecipitated with HSP90, and the knock-down of HDAC6 by its siRNA induced the acetylation of HSP90 and alpha-tubulin. Depletion of HDAC6 levels also inhibited the binding of HSP90 to ATP, reduced the chaperone association of HSP90 with its client proteins, e.g. Bcr-Abl, and induced polyubiquitylation and partial depletion of Bcr-Abl. Conversely, the ectopic overexpression of HDAC6 inhibited LAQ824-induced acetylation of HSP90 and alpha-tubulin and reduced LAQ824-mediated depletion of Bcr-Abl, AKT, and c-Raf. Collectively, these findings indicate that HDAC6 is also an HSP90 deacetylase. Targeted inhibition of HDAC6 leads to acetylation of HSP90 and disruption of its chaperone function, resulting in polyubiquitylation and depletion of pro-growth and pro-survival HSP90 client proteins including Bcr-Abl. Depletion of HDAC6 sensitized human leukemia cells to HAA-HDIs and proteasome inhibitors (9.) Chromatin-modifying enzymes such as histone deacetylases (HDAC) facilitate a closed chromatin structure and hence transcriptional repression. HDAC are commonly affected in human cancer diseases. Thus, inhibition of HDAC represents a novel therapeutic approach. Several studies have shown that HDAC inhibitors strongly activate the expression of the cyclin-dependent kinase inhibitor p21(cip1/waf1) through (i) enhanced histone acetylation around the p21(cip1/waf1) promoter and (ii) the Sp1 sites on the p21(cip1/waf1) promoter releasing the repressor HDAC1 from its binding. p21(cip1/waf1) expression is regulated in a p53-dependent and p53-independent manner. The decision if p21(cip1/waf1) up-regulation results in cell cycle arrest or apoptosis, decides about the therapeutic efficacy of an anti-cancer treatment with HDAC inhibitors (10.) Sulforaphane (SFN), a compound found at high levels in broccoli and broccoli sprouts, is a potent inducer of phase 2 detoxification enzymes and inhibits tumorigenesis in animal models. SFN also has a marked effect on cell cycle checkpoint controls and cell survival and/or apoptosis in various cancer cells, through mechanisms that are poorly understood. We tested the hypothesis that SFN acts as an inhibitor of histone deacetylase (HDAC). In human embryonic kidney 293 cells, SFN dose-dependently increased the activity of a beta-catenin-responsive reporter (TOPflash), without altering beta-catenin or HDAC protein levels. Cytoplasmic and nuclear extracts from these cells had diminished HDAC activity, and both global and localized histone acetylation was increased, compared with untreated controls. Studies with SFN and with media from SFN-treated cells indicated that the parent compound was not responsible for the inhibition of HDAC, and this was confirmed using an inhibitor of glutathione S-transferase, which blocked the first step in the metabolism of SFN, via the mercapturic acid pathway. Whereas SFN and its glutathione conjugate (SFN-GSH) had little or no effect, the two major metabolites SFN-cysteine and SFN-N-acetylcysteine were effective HDAC inhibitors in vitro. Finally, several of these findings were recapitulated in HCT116 human colorectal cancer cells: SFN dose-dependently increased TOPflash reporter activity and inhibited HDAC activity, there was an increase in acetylated histones and in p21(Cip1/Waf1), and chromatin immunoprecipitation assays revealed an increase in acetylated histones bound to the P21 promoter. Collectively, these findings suggest that SFN may be effective as a tumor-suppressing agent and as a chemotherapeutic agent, alone or in combination with other HDAC inhibitors currently undergoing clinical trials (11.)

Sulforaphane’s ability to do everything we just discussed should make you want to start eating your broccoli as well as possibly supplementing with a good sulforaphane product (which is very few and fair between.) In terms of an applicable dosage, it seems that right around the 30mg per day mark is proven in literature to be beneficial (with some even dosing it up to double based on their body weight being higher.) Sulforaphane’s benefits are endless and is a must have health AND ergogenic aid supplement for any serious competitor (or at least it is in my eyes.)


  1. Protein oxidation and aging. E. R. Stadtman. Science. 1992 (
  2. Sulforaphane Activates Heat Shock Response and Enhances Proteasome Activity through Up-regulation of Hsp27. Nanqin Gan, Yu-Chieh Wu, Mathilde Brunet, Carmen Garrido, Fung-Lung Chung, Chengkai Dai, Lixin Mi. J Biol Chem. 2010 (
  3. Role of increased expression of the proteasome in the protective effects of sulforaphane against hydrogen peroxide-mediated cytotoxicity in murine neuroblastoma cells. Mi-Kyoung Kwak, Jeong-Min Cho, Bo Huang, Soona Shin, Thomas W. Kensler. Free Radic Biol Med. 2007 (
  4. Sulforaphane induced adipolysis via hormone sensitive lipase activation, regulated by AMPK signaling pathway. Ju-Hee Lee, Myung-Hee Moon, Jae-Kyo Jeong, Yang-Gyu Park, You-Jin Lee, Jae-Won Seol, Sang-Youel Park. Biochem Biophys Res Commun. 2012 (
  5. Identification and role of the basal phosphorylation site on hormone-sensitive lipase. A. J. Garton, S. J. Yeaman. Eur J Biochem. 1990 (
  6. 5-Aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside-induced AMP-activated protein kinase phosphorylation inhibits basal and insulin-stimulated glucose uptake, lipid synthesis, and fatty acid oxidation in isolated rat adipocytes. Mandeep Pinky Gaidhu, Sergiu Fediuc, Rolando Bacis Ceddia. J Biol Chem. 2006 (
  7. Sulforaphane causes a major epigenetic repression of myostatin in porcine satellite cells. Huitao Fan, Rui Zhang, Dawit Tesfaye, Ernst Tholen, Christian Looft, Michael Hölker, Karl Schellander, Mehmet Ulas Cinar. Epigenetics. 2012 (
  8. Sulforaphane attenuates hepatic fibrosis via NF-E2-related factor 2-mediated inhibition of transforming growth factor-β/Smad signaling. Chang Joo Oh, Joon-Young Kim, Ae-Kyung Min, Keun-Gyu Park, Robert A. Harris, Han-Jong Kim, In-Kyu Lee. Free Radic Biol Med. 2012 (
  9. Inhibition of histone deacetylase 6 acetylates and disrupts the chaperone function of heat shock protein 90: a novel basis for antileukemia activity of histone deacetylase inhibitors. Purva Bali, Michael Pranpat, James Bradner, Maria Balasis, Warren Fiskus, Fei Guo, Kathy Rocha, Sandhya Kumaraswamy, Sandhya Boyapalle, Peter Atadja, et al. J Biol Chem. 2005 (
  10. Histone deacetylase inhibitors: signalling towards p21cip1/waf1. Matthias Ocker, Regine Schneider-Stock. Int J Biochem Cell Biol. 2007 (
  11. A novel mechanism of chemoprotection by sulforaphane: inhibition of histone deacetylase. Melinda C. Myzak, P. Andrew Karplus, Fung-Lung Chung, Roderick H. Dashwood. Cancer Res. 2004 (